Day 1 :
King’s College Hospital NHS Foundation Trust | UK
Royce P Vincent (MBBS, MSc, EuSpLM, FRCPath, MD) is a Consultant Chemical Pathologist at King’s College Hospital NHS Foundation Trust and an Honorary Senior Lecturer at King’s College London, UK. He is the Clinical Lead for Biochemistry and Parenteral Nutrition services. He obtained his MD (Res) at Imperial College London. His research interests are in clinical nutrition, obesity and endocrinology. He has published multiple original research and review articles and is serving as an international editorial board member for Translational Metabolic Syndrome Research.
Type 2 diabetes is a pandemic afflicting more than 400 million people, with estimates of 650 million cases by 2040. Even with significant advances in pharmaceutical agents recently shown to reduce cardiovascular events, many patients with diabetes fail to achieve glycaemic treatment goals required to reduce micro and macrovascular complications. Metabolic surgery (bariatric surgery) is currently the most effective treatment to achieve significant and sustained weight loss in morbid obesity. There is now growing evidence of long-term remission of type 2 diabetes after metabolic surgery hence, the second Diabetes Surgery Summit (DSS-II), an international consensus conference, developed global guidelines that recommend inclusion of metabolic surgery among interventions for selected patients with type 2 diabetes and obesity. These recommendations have now been endorsed by more than 50 organisations worldwide, including major national and international diabetes and surgical societies. However, the pathophysiology of improved glucose metabolism after metabolic surgery remains poorly understood. Bile acid pool and composition are altered following certain metabolic surgeries. Thus, bile acids have emerged as a potential contributor to the improved glycaemic control after the procedures. Bile acids are the main component of human bile and have traditionally been considered mediators of lipid absorption and cholesterol metabolism, facilitated by their amphipathic nature. In recent years the discovery that specific bile acids differentially activate the G protein-coupled membrane receptor (TGR5) and the nuclear receptor, farnesoid X receptor (FXR), has identified bile acids as complex metabolic molecules that play a role in numerous pathways. This session will provide an overview of our current understanding of the interplay between bile acids and incretin (gut) hormones, the laboratory analysis of bile acids and its potential role in improving glycaemic control and remission of type 2 diabetes.
University Grenoble Alpes | France
Serge Bottari, obtained his M.D. and Ph.D. degrees at the Free University Brussels, Belgium. He specialized in OB/GYN and Biochemistry and was a Post-Doctoral Fellow and Research Associate at UC San Francisco. After having been a project leader at Sandoz and CIBA-Geigy, he became Professor of Cell Biology at the Medical School in Grenoble and Head of Endocrine Biology in 1993. His articles in premium journals have been cited more than 4000 times and he is a member of several editorial boards. He also holds several patents. His current work focuses among others on the molecular mechanisms involved in insulin resistance and on the development of novel diagnostic tools.
Insulin resistance (IR) affects more than half of the adult population worldwide. Type 2 diabetes (T2D), which often follows in the absence of treatment, affects more than 400 million people and represents more than 10 % of the health budget in industrialized countries. A preventive public health policy is urgently needed in order to stop this constantly progressing epidemic. Indeed, early management of IR does not only strongly reduce its evolution towards T2D but also strongly reduces the appearance of cardiovascular comorbidity as well as that of associated cancers. There is however currently no simple and reliable test available for the diagnosis or screening of IR. We therefore developed an ELISA for the quantitative determination of a novel circulating biomarker of IR, IRAP. IRAP is associated with and translocated in a stoechiometric fashion together with GLUT4 to the plasma membrane in response to insulin in skeletal muscle and adipose tissue. Its extracellular domain is subsequently cleaved and secreted in the blood stream. In T2D, IRAP translocation in response to insulin is strongly decreased. Our patented sandwich ELISA is highly sensitive and specific, robust and very cost-effective. Results of pilot studies indicate an excellent correlation between serum IRAP levels and insulin sensitivity. We therefore believe that serum IRAP is a direct marker of insulin sensitivity and that the quantitative determination of its plasma levels should allow large-scale screening of populations at risk for IR and T2D, thereby allowing the enforcement of a preventive health policy aiming at reducing this epidemic. Similarly, simple companion tests alowing the assessment of the efficacy of novel drugs aimed at improving insulin sensitivity do not exist yet. As such serum IRAP appears as a useful alternative to the euglycemic hyperinsulinic clamp which is very tedious, expensive and requires experencied teams, to monitor insulin sensitivity in human in clinical trials and therapeutic trials.